1.0 OBJECTIVE
This policy described the framework within which the Quality of HAPL products will be assured.
2.0 SCOPE
This policy is applicable to HAPL facilities including R and D Production and Distribution.
3.0 GUIDEDENCES/DIRECTIVES/REGULATIONS
3.1 The local Health Authority Guidelines/Directives/Regulations should be the basis for the development of Quality Guidelines/ Procedures. The HAPL Quality Policiese are written based on á realistic interpretation of international regulation. These standards will be interpreted though Policies Guidelines ánd Procedures.
3.2 The policies that are developed by QÁ should be translated, using common sense and appropriate local management review, into pracival procedures (SOPs) that are flexible enough to assure product quality without overcomplicating Production and Quality Control.
3.3 Significant difference in operations from those described by HAPL Quality Policies must be reviewed and approved by local management and QÁ variance/deviation procedure.
3.4 Production and testing facilities should have procedures (SOPs) applicable to their functions. The following is á thorough but not exhaustive list of required procedures(SOPs).
A Facility Certification
This procedure (SOP) should require that the products and production quantities (deve-
elopement batches/batches manufactured/lots packaged) be defined for existing facilities, for additions/modification to existing facilities and for justifying new facilities.
This information is necessary as á basis of design in order to specify the type and size of the sturcture, the layout and interior finishes, the support systems, the equipment
and instruments required for production, the laboratory requirement and the administrative space necessary. This information also serves as the foundation for the Drug Master File(Type ) and/or Plans Master File.
B Product Development procedures cover the methodology and documentation required to support each stags of R and D actévity up to the point of clinical trials. These SOP's
should stress documentation to back up the selection of raw materials and to describe the development of processes. The principles of GMP are applicable to the manufacture of clinical trial supplies.
C Clinical Trial procedures describe the activities inco-porates in Good Clinical Practice guideline published by world health authorities and regulatory agencies.
D Technology Transfer is the process of handing over á production process, and the associated testing methodology from one site to another i.e.from R and D and the acceptance by the production facility.
E Production Specifications are initially developed by R and D reviewed by Production and Quality Control;approved by QÁ based on the recommendations of the
developers and reviewers.
F Test Methods are developed by R and D validated by R and D and Production and where applicable by health authorities (i.e.USP) and approved by QA.
G Product Approval for Sale documents are generated by Regulatory Affaire based on appropriate filings that have been approved by the local Regulatory Agency(ies). The
approval is granted only for those facilities which have been certified, for those processes which have been valida-Ted, for those sources of raw materials which have been approved, and for which Production and Quality Departments have been deemed acceptable to adequately product and control the products.
H Equipment and Process Selection procedures should be in place to establish the mechanism kfor choosing the optimum equipment to meet the processing and volume requirements of not only the local site but also taking into consideration
back-up and alternative production objectives of the co..
I Training programmer for orientation to HAPL Quality and job skills training should be developed, including adequate documentation.
J Contractors and Suppliers of all materials and products used in HAPLfacilities should be formally approved» including but not limited to raw material and pa- ckage component suppliers, construction contractors,clan- inç services, exterminators, food service supply companies, general contractors, equipment and process specialists, raw material vendors, finished goods contractors and outside teasing laboratories
K Raw Material procedures should cover the receipt, qua- rantine, sampling and/or testing, release/reject, and st-orage of active and inactive ingredjents.
L Process Validation procedures should describe the equi-pment and process parameters necessary to conistently pro-duce acceptable product» this is usually composed of these
basis steps» specification, installation/operational qual-ification, place or finished product testing.
M Produce Validation procedure should detail the equipment, process, parameters, sampling, product specifications and test methods used to validate á production process for á specific product. Each product formulation produced using á unique process and equipment must be validated as well as processes/products transferred from one facility to another.
N Cleaning procedures are requires for the facility in General, the warehousing, manufacturing and packaging areas in particular, including sanitation and per control.
O Calibration and Maintenance programmes are necessary for the facility, all systems in facility (particularly those in the processing area) and at equipment and inst-rument. Á scheduled maintenance programme is requires including kegs for all processing, labeling and packag, inç equipment.
P Document Control procedures need to be in place to assure that the registered details of development, proce-ssing, packaging, testing and marketed products veillance are being adheres to and update as approved changes occur
Q Change Control system should be set up to authorize necessary modifications to facilities systems processes specifications and test methods. Á formal management review and approval process will assure appropriate just- ification for changes.
R Production Control procedures should encompass the system of controlling the receipt, disposition and storage of raw materials and package components» master document
control and working document distribution for the dispen-sing, manufaturinç and packaging process, and the distri- bution tracking system for use in case of recall
S Sampling and Testing procedures are requires for raw materials, package components, in-process production, fin-ished products,reserve samples and stability samples.
Specific procedure should be in place for validation samp-ling, process modification, process problems and investig-ation of material at any stage that fails to pass specifi-
cations.
T Quality Control Laboratories require procedures covering the operation of the analytical, biological, and microbio-logical and other departments. These procedures should
include laboratory management, specification and methods Control, laboratory set-up for requires testing (equipment instument, hoods, clean/sterile areas, etc) The standards
reagents, chemicals required testing procedures» review of test results retest procedures management review requi-rements and documentation control.
U Documentation Review and Material Disposition proced- res should be set up for the review of the requires docume-ntation for acceptance or rejection for raw materials,
package components, in-process products, finished goods produced internally or contractor produced finished goods. The documentation package should include all pertinent in- formation such as purchase orders, receiving reports, sa- mpling documentation, test reports, data summaries, inve-satiation» reports and production and packaging records,as appropriate. This review should be done by the receiving warehouse, manufacturing and packaging personnelin conjunction with their Quality Control counterparts. The previously reviewed documentation package should be sent to
Quality Assurance for final review and material disposition (release or reject).
V Material Disposition procedures should be developed to review the appropriate documentation pertaining to the quarantine, release or rejection of material at any
stage. Quality Assurance procedures should include á checklist of documents required for the evaluation of each item within the categories of raw materials, package
components, work-in-process materials and finished goods. Critical processing parameters, including variances, deviations, failing test data, rejections and investing,
ation report should be checked by QÁ before determining material disposition.
W Material Rejection/Investigation Report procedures should be developed for the investigation of all failing test results and material rejections. Á summary report
including investigation of all associated materials, pro- cesses, batches and lots should be submitted to QÁ by the involved receiving, warehousing, manufacturing and packa-
ginç personnel and their counterparts in Quality Control.
X Stability Programmes should be developed for active ingredients, excipients, in-process materials(if stored) and finished goods. Those programmes should include res-
erve samples stored at room temperature and ambient humi-dity and stability samples that are stored at various elevated temperatures and humidity levels to artificially
accelerate the ageing of stability samples. The Stability Programme should include provision for periodic routine and alert reports for potential product instability.
Y Medical Complaint procedures should be prepared to deal with concerns about Product Safety and efficacy and patient medical problems. Those procedures should be
developed by Medical Affairs to compliment the Product Complaint procedures developed by QA. All correspondence relating to product complaints of á technical nature shold be archived by QA.
Z Product Complaint procedures should be developed for the appropriate investigation of packaging, labeling and product complaints. The procedures should include
corrective action recommendations and appropriate corres-pondence with the originator of the complaint or contact person. The procedures should be developed by QÁ and
compliment the medical procedures. All correspondence should be archived by QA.
a Product Recall procedures should be in place to desc-ribs the process for reaching the desiccation to recall, to define the appropriate notification to the health autori-
ties and to permit the traceability of all raw materials and package components through processing the finished product. Finished product tracing should extend to theinitial recipient and subsequent distribution.
b Annual Product Review procedures should be establi-shed to review the various aspects of products form á twelve(12) month overview perspective. The annual review
should include but not be limited to production problems, test data rends, process variations and deviations, rejec-tion, stability problems and product complaints. The
reviews should be conducted by QÁ and results should be reported to management.
c Inteernal/self Audit procedures should be developed
d Information about the site. Within that document there should be information about the facility, management, products, processes, procedures (SOPs) validation protocols and recent Production and Quality Control Data.
